AB0403 LONGITUDINAL ANALYSIS OF CHANGES IN THE FINE ARTICULAR STRUCTURE BY CTLA4-IG USING HR-PQCT IN RHEUMATOID ARTHRITIS
Authors: N. Iwamoto, K. Chiba, S. Sato, K. Watanabe, K. Shiraishi, N. Ohki, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Although the clinical effect of CTLA4-Ig (abatacept: ABT) on rheumatoid arthritis (RA) has been shown by a several kinds of large scale clinical trials and postmarketing surveillances, detail of its effect at a local joint has not been sufficiently analyzed. Recently, it has been shown that CTLA4-Ig has not only inhibition effect on T-cell activation but also has inhibition effect on osteoclast differentiation by directly affecting osteoclast precursors,<sup>[1]</sup> therefore analysis of the effect on changes in the bone structural at an actual clinical site has been expected. A novel imaging test method of High Resolution peripheral Quantitative CT (HR-pQCT) can detect fine structure of bones that could not have been detected in the past and it can evaluate not only conditions of joint destruction but also periarticular osteoporosis. <h3>Objectives</h3> To compare the changes in fine articular structure including bone erosion and micro-architecture by ABT and csDMARD in patients with RA using HR-pQCT. <h3>Methods</h3> In this open-label, parallel-group study, twenty patients who started newly csDMARD and 15 patients who started ABT were enrolled. Fine articular structure in 2,3 metacarpal head were assessed by HR-pQCT every 6 month for 12 months. Synovitis was assessed by musculoskeletal ultrasound (MSUS) and magnetic resonance imaging (MRI) of wrist and fingers. We also measured the bone mineral density (BMD) of lumber spine. The estimated difference in adjusted mean and mean (ABT–csDMARD group) and 95% CIs and P-values were calculated using a linear mixed model with treatment group, allocation factor, baseline disease activity, observation time-point, and treatment group × observation time-point as fixed effect, patients as random effect, and baseline value as covariates. <h3>Results</h3> Baseline characteristics including disease activity were similar between the ABT and csDMARD groups. The mean Δdisease activity scores (DAS)28-ESR from baseline to 12 months were −1.61 (ABT) and −1.71 (csDMARDs). The estimated difference of mean changes in erosion volume, depth and width of 2,3 metacarpal head between ABT and cs DMARDs group were -1.86mm<sup>3</sup>, -0.02mm and -0.09mm, respectively (Table 1). During observational period (12 months), only one new erosion detected by HR-pQCT appeared, and 14 erosions were repaired in ABT group, whereas, in csDMARD group, 5 new erosions appeared, and 5 erosions were repaired. Regarding synovitis, changes in synovitis score defined by MSUS and the RA-MRI score (RAMLIS) were similar between these two groups. Compared with patients in the csDMARD group, those in ABT group had better bone micro-architectures improvement (Table 1). In the other hand, % change of BMD of lumbar at 12 months were less improved in ABT group as compared csDMARDs group (0.17%, 1.82%, respectively). <h3>Conclusion</h3> Our results indicated that the ABT could repair bone erosions and had better inhibitory effect of bone erosion, improvement periarticular osteoporosis as compared with csDMARD treatment regardless of improvement of disease activity, synovitis and progress of systemic osteoporosis. Thus, CTLA4-Ig treatment might be beneficial not only in terms of inhibition of bone erosion but also improvement of bone micro-architecture. <h3>Reference</h3> [1] Bozec A, Zaiss MM, Kagwiria R, Voll R, Rauh M, Chen Z, et al. T cell costimulation molecules CD80/86 inhibit osteoclast differentiation by inducing the IDO/tryptophan pathway. Sci Transl Med. 2014 May 7;6(235):235ra60. <h3>Acknowledgements</h3> This work is supported by the Bristol-Myers Squibb K.K. and ONO PHARMACEUTICAL CO., LTD. <h3>Disclosure of Interests</h3> Naoki Iwamoto Grant/research support from: ONO PHARMACEUTICAL CO., LTD., Ko Chiba: None declared, Shuntaro Sato: None declared, Konosuke Watanabe: None declared, Kazuteru Shiraishi: None declared, Nozomi Ohki: None declared, Atsushi Kawakami: None declared.